Quinazoline rearrangement

Ether groups in the benzene ring of quinazoline behave as in ethers of homocyclic aromatic compounds, e.g., they can be demethylated with anhydrous aluminum chloride. Allyl ethers also undergo a Claisen rearrangement/ ... 

The rearrangement of l-methyl-2-arainopyrimidine to 2-methyl-aminopyrimidine with alkali has been recently observed in amino-quinazolines. The following rearrangement proceeded in high yields when R was Me, Et, Pr , Ph, and p-MeOC6H4 ... 

Another dihydro derivative has been described in connection with medicinal chemical studies. Thus, reaction of 2-(chloromethyl)quinazoline-3-oxide (3) with hydrazine gives hydr-oxytriazocinamine 4 (and not a diazepine derivative as originally assigned), vigorous acetylation of which results in a rearrangement to give oxazolotriazocine 5.10... 

Reaction of 2-amino-benzyl alcohol and 2-chloroH-phcnylaminopyrimidinc forms the intermediate cation 204, which contains ene and iminium functionalities and undergoes electrocyclic rearrangement to the 2-phenylamino-6//-pynmido[2,l-2 ]quinazoline 205 (Scheme 32). The cation 204 is stabilized by the aryl groups. The 2-NHPh stmcture of the product was confirmed by 111 NMR spectroscopy <2002TL1303>. 

New rearrangements of 2-imino-2//-l-benzopyran-3-carboxamides under the action of anthranilic acid as an N-nucleophile have been revealed. Depending on the conditions 2-(2-oxo-2//-l-benzopyran-2-yl)-3//-quinazolin-4-ones or 2-oxo-2//-l-benzo-pyran-3-((V-2-carboxyphenyl)carboxamides were found to be the products. 

Treatment of quinazoline 3-oxide with amines gives the rearrangement product, 1,4-benzodiazepine. 

The conversion of 63 into 65 involves a double ANRORC-type rearrangement reaction first a rearrangement of 63 into the [l,2,4]-triazino [3,4-6]quinazoline 64 [by bond breaking in 63, rotation and recyclization], followed by a second rearrangement of 64 into 65 both rearrangements occur according to the same mechanism as that presented in Scheme IV.24. It has been recorded that surprisingly the V-methyl derivative of 63 is unaffected when heated in acetic anhydride/sodium acetate however, the N-... 

Also in the quinazoline series Dimroth rearrangements have been reported. 2,3-Dihydro-2-imino-3-methylquinazoUne (81) rearranges very easily (alkali, room temperature) into 2-methylaminoquinazoline (68AJC2813) (Scheme IV.33a). 

The constitutionally isomeric 3-substituted (l//,3//)-quinazoline-2,4-diones and 2-phenylimino-4//-3,l-benzoxazin-4-ones are easy to distinguish via their El mass spectra (93RCM374). For quinazolinediones, the most striking feature is the loss of CO2, proving that a rearrangement due to anilino migration must occur. 

Cycloaddition of nitrile ylides (204) to nitroso compounds gives mixtures of (205) and (206), which both slowly rearrange to quinazolines (207) (Scheme 89) <77CB605>. 

Thermally promoted Claisen rearrangement of simple allyloxypyrimidines is difficult to effect, but is more common with quinazolines where it has been used to prepare allyl derivatives substituted in the carbocyclic ring < 1996HC(55) 1 >. An attempted amino-Claisen rearrangement of a 4-allylaminopyrimidine was unsuccessful <2005AJC368>. 

Dialkylquinazolines 825 are available by microwave-assisted amination and ring closure of 2-acylamino phenyl-ketones 824 with ammonium formate <20070L69>. The 2-aminophenyl ketone precursors of the amides 824 are available by a photochemically induced Fries rearrangement of anilides 823, which enables a variety of different alkyl substituents to be incorporated at the 4-position of the quinazoline <20070L69>. 

Hu et al. (91MI1) report the Dimroth rearrangement of 2-hydrazino- to 2,3-diamino quinazolin-4-ones under catalysis of carboxylic acid derivatives this reaction is followed by an in situ cyclization in which the same carboxylic acid derivatives serve as C,-synthons. l-Acylamino-2-alkylthiopyrimidines are hydrazinolyzed and cyclized to 3-amino-1,2,4-triazolofl, 5-a]pyrimidinium salts (89EGP270711). 

Another group of acid-catalyzed rearrangements involves cleavage of the 3,4-bond followed by cyclization between positions 2 and 4, for example the conversion of (218) to the quinazoline carboxaldehyde (219). Similar reactions are given by (220) and (221). 

Spiro 1 - methylsulfony 1-3//-indoline -3,2 -[3, 5 -di(ethoxycarbonyl)-4 -methyl-2 //-pyrrole] (64) underwent molecular rearrangement with 100% H3PO3,60% H2SO4, or by heating at 200° to 1,3-di(ethoxycarbonyl)-2-methyl-6-methylsulfonyl-4,5-dihydropyrrolo[ 1,2-c]quinazoline (65)... 

Treatment of 4-hydroxy-l-(2-pyridyl)quinolin-2-one (442) with sulfuryl chloride gave 3,3-dichloro-l-(2-pyridyl)quinoline-2, 4-dione (443) which, upon treatment with sodium carbonate, rearranged to pyrido[2,l- >]quinazolin-l 1-one (440) (79CB3424). 

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